Persons with HBsAg-positive chronic hepatitis are being enrolled in a prospective study of this disease. Fifteen persons have been entered into this study, 12 of whom have been followed for at least 6 months, 9 of whom have had liver biopsies. At the start all 15 had elevated serum enzymes and were HBsAg positive; 12 had HBeAg and 11 DNA-polymerase. On follow-up, all have remained HBsAg positive but two have had a spontaneous fall HBsAg titer and both have lost HBeAg. One of the two has become DNA-polymerase negative. The remaining patients have had stable levels of HBsAg, HBeAg and DNA-polymerase. In individuals with stable hepatitis B virus markers, trials of antiviral agents are being planned. A new drug - phosphonoformate - is currently being evaluated in HBsAg positive chimpanzees by Dr. Purcell's laboratory. Applications with the pharmaceutical company (Astra) have been made to start a trial of this drug in human chronic HBsAg carriers.